The contribution of microbiome-mirna interaction in the development of diseases.
Author: Fathima Sible D Souza
WHAT IS HUMAN GUT MICROBIOME?
The human gastrointestinal tract, which is also known as the digestive tract, is home to a large number of bacteria, fungi and viruses. These microorganisms are collectively referred to as the microbiome. In fact, there are over trillions of microbiomes in the human body, and the number of bacterial cells in the human body surpasses the number of human cells by 10 times. There are nearly 1000 different species of gut microbiome that play a major role in balancing our health and cause of disease.
MICROBIOME AND MICROBIOTA ARE NOT THE SAME
Although the words microbiota and microbiome sound similar, their meanings differ slightly. Microbiota refers to the living microbe that occupies specific habitats, such as the oral, skin, and intestinal parts of the body. On the other hand, microbiome takes into account the variety of genomes of the microorganisms in an environment, the structural component, metabolites produced, and other factors in a population of microorganisms, making it a wider spectrum compared to the microbiota.
COMPOSITION OF A HEALTHY GUT MICROBIOTA
The gut microbiota is composed of various microorganisms, predominantly anaerobes which can grow in the presence or absence of oxygen. However, some anaerobes can tolerate a certain level of oxygen. Over 50 different phyla are associated with the GIT, but 6 phyla dominate the gut microbiota. They are,
-Firmicutes, -Bacteroidetes, -Fusobacteria, -Verrucomicrobiota, -Proteobacteria, and -Actinobacteria. Among these, Firmicutes and Bacteroidetes are found in larger numbers compared to the others.
THE ROLE OF GUT MICROBIOME IN HEALTH
The gut microbiome starts to affect an individual’s life from the moment of birth. As the person grows, the microbiome diversifies, and the food we consume plays a significant role in this. It is believed that the more diverse the gut flora, the better the individual’s health. Even though they are associated in the GIT they have considerable effect on other parts of the body. They have an impact on
- Digestion of the food
- Control of immune health
- Weight gain
- Gut-related diseases like Inflammatory bowel syndrome& Inflammatory bowel disease
- Heart health- by promoting the production of good cholesterol (HDL) and triglycerides
- Helps in Blood sugar control and Brain Health
WHAT IS micro RNA?
Micro RNA is a type of RNA molecule that is approximately 22 nucleotides in length and does not code for protein. mi RNAs regulate gene expression by binding to messenger RNA (mRNA) molecules with complementary sequences, thereby preventing their translation and potentially leading to their degradation. This process is known as post-transcriptional gene control and can result in the silencing of the target gene, ultimately reducing its expression. Some plants, animals, and viruses naturally contain miRNA, mainly in cells and the bloodstream.
miRNA- What they do?
- Degrades Mrna
- Hence preventing the process of translation
APPLICATIONS OF miRNA
- As Biomarkers for the identification of disease: Dysregulation of microRNA is associated with cancer development. Therefore, microRNA expression can be used as a biomarker for identifying and prognosing various types of cancer, such as breast cancer.
- Drug development: Modifying miRNA using antisense oligonucleotide is a new approach for treating disease as it can change mRNA expression, opening new doors for drug discovery.
- Can also be used in the study of cell metabolism, cell proliferation, apoptosis
- Personalized medication: miRNA expression varies in different individual depending upon the illness, progression and other factors. Individual miRNA analysis can make it possible to introduce customized medication to enhance patient outcomes and reduce side effect.
- Agricultural biotechnology: Modifying microRNA expression in plants can enhance agricultural productivity, disease resistance, and stress tolerance in changing environments.
Dysregulated microRNA leads to the development of diseases.
MicroRNAs are small molecules that help regulate the expression of genes. Dysregulation of microRNA has been linked to a variety of diseases, such as cancer, cardiovascular disease, cardiac failure, inflammatory disease, neuronal disorders, autoimmune disorders, and skin disorders. The loss or overabundance of microRNA has been linked to these clinically significant conditions. Dysregulation can be caused by a single point mutation in miRNA or in the corresponding target mRNA. In recent years, miRNAs have made significant advances in the detection and treatment of various disorders, offering hope for the future.
THE MECHANISM INVOLVED INTERACTION BETWEEN GUT MICROBIOME AND miRNA
- Involvement of microbial metabolites-miRNA
The interaction between microbiome and miRNA involves complex molecular and cellular pathways. Although this field is still developing, some important interactions have been identified to explain the relationship.
The metabolites of gut microbiota, such as Lipopolysaccharides, amyloids, and butyrate, have been found to affect the host’s gene expression, including microRNA. This suggests that gut microbiota can influence miRNA expression.
- Epigenetic modification:
The metabolites that the microbiome produces play an important role in modifying the host’s epigenetics. DNA methylation can lead to the destruction of DNA fragments without altering the DNA sequence, while Histone modification is another form of epigenetic modification. This process involves modifying the histone proteins with PTMs, known as the Histone code, which can cause changes in gene expression, leading to modifications in miRNA.
- Immune response by the Host: The human immune system is one of the factors that determine the microbiome’s diversity and composition. To certain microbial stimuli, immune cells can produce dendritic cells and macrophages which in turn produce miRNA regulating the production of cytokines. These miRNAs produced by the lymphocytes therefore influence the ecology of the microbiome by targeting the desired gene.
The exact interaction between these mechanisms still needs to be researched to provide more evidence of the gut-microbiome relationship and to develop potential new therapeutic targets.
Connection Between Microbiome-miRNA Dysregulation and Diseases
The dysregulation between microbiome-miRNA results in the development and progression of various disease. Some majority of the disease associated with the imbalanace/dysregulation is listed below
- Cardiovascular disease: gut microbiome metabolites are known to influence the occurrence of different cardiovascular diseases like atherosclerosis, platelet activity, thrombosis, hypertension and others. The gut microbiota has the ability to effect RNA genes related to vascular miRNA classes miR-204, miR-108 which can either decrease or increase the risk of CVD.
- Intestinal Homeostasis: Intestinal homeostasis is studied through miRNA expression in the Intestinal epithelial cells. The elevated number of IEC cells results in changes in the expression of miRNA influencing cell death, apoptosis
- Cancer: Gut microbiome-miRNA is also associated with cancer development. For example, In colon cancer miRNA profile of stool is used as a noninvasive biomarker for detecting carcinoma. A gut microbiome profile of colon cancer patients had an abundance of Alistipes putredinis while Faecalibacterium prausnitzii was common in stool samples from controls and individuals with adenoma condition.
- Brain interaction: The main causative factor associated with gut microbiome-miRNA is the dysfunction of gut immune system resulting in the dysregulation of mast cells and macrophages. This is mainly because of the inhibition expression of micro-RNA.
The Promising Future of Targeting Microbiome-miRNA Interactions in Therapeutic Interventions for Diseases.
A recent study has shown that targeting microbiome-miRNA interactions in therapeutic treatments for diseases, specifically breast cancer, is a promising approach. The study highlights the potential of interactions between the gut microbiota and flax seeds, which are known for their high lignan and fiber content, to alter the expression of microRNAs (miRNAs) in breast cancer cells. These findings provide insight into new approaches for cancer prevention and therapy by revealing the complex link between gut microbiota, nutrition, and miRNA expression.
CONCLUSION
The gut microbiome and microRNAs (miRNAs) have a complex interaction that affects human health and disease. This interaction is linked to various illnesses, including cancer, cardiovascular disease, neurological disorders, and intestinal problems. Understanding this interaction presents opportunities for personalized medicine and therapeutic interventions. Studies have shown that regulating miRNA expression through dietary interventions may lead to novel therapy development. Ultimately, this interaction may lead to new diagnostic biomarkers and therapeutic approaches that improve patient outcomes and adva